YY1 (yin-yang 1, also called NF-E1, delta, or UCRBP) is a GLI-Kruppel-type zinc finger nuclear factor that is able to repress, activate and initiate transcription depending on promoter architecture and the cellular environment (1). YY1 can activate or repress the c-fos promoter depending on the orientation of a YY1 recognition element in the promoter. YY1 can switch between an activator or repressor of the human papillomavirus type 18 promoter depending on the integrity of a distinct element upstream in the promoter (2). YY1 competes with NF-kappaB for overlapping binding sites in the serum amyloid A1 promoter and inhibits promoter activity by passive means. Similarly YY1 can antagonize the interaction of SRF to overlapping binding sites in the actin promoter. The four GLI-Kruppel-related zinc fingers at the carboxyl terminus of YY1 constitute a strong repression domain (3). YY1 functionally interacts with a large number of other key transcriptional regulators, such as Sp1, c-Myc, adenovirus E1A, the cAMP response element-binding protein-related factor, p300, and components of the general transcriptional apparatus including the large subunit of RNA polymerase II and transcription factor IIB (TFIIB) (4,5). The capacity of YY1 to bend DNA when it binds the promoter facilitates direct contact between regulatory proteins. YY1 can interact with histone deacetylases to repress the activity of certain promoters, including the human immunodeficiency virus type 1 long terminal repeat (6), thereby modulating histone and chromatin structure.
The pathogenesis of common vascular disorders such as atherosclerosis and restenosis after balloon angioplasty is believed to be mediated at least in part by phenotypic changes involving smooth muscle cells of the artery wall. These cells normally adopt a “contractile” phenotype (7) in the vessel wall, but upon activation (such as mechanical injury imparted by angioplasty balloons), these cells become “synthetic” (7) and contribute to developing lesions by migrating, proliferating, producing extracellular matrix, and elaborating and responding to a myriad of growth-regulatory molecules (8). YY1 can repress the promoters of a wide spectrum of pro-atherogenic genes, including cytokines, hormones and growth factors (9-14). As such, YY1 may play an atheroprotective role in the artery wall. However, whether YY1 is even expressed in the artery wall or is regulated in the adaptive response to injury is presently not known, nor is whether YY1 can influence the growth of smooth muscle cells or other cell types.